Document Detail

Sequence dependence of chromosomal R-loops at the immunoglobulin heavy-chain Smu class switch region.
MedLine Citation:
PMID:  17562862     Owner:  NLM     Status:  MEDLINE    
The mechanism by which the cytidine deaminase activation-induced deaminase (AID) acts at immunoglobulin heavy-chain class switch regions during mammalian class switch recombination (CSR) remains unclear. R-loops have been proposed as a basis for this targeting. Here, we show that the difference between various forms of the Smu locus that can or cannot undergo CSR correlates well with the locations and detectability of R-loops. The Smu R-loops can initiate hundreds of base pairs upstream of the core repeat switch regions, and the area where the R-loops initiate corresponds to the zone where the AID mutation frequency begins to rise, despite a constant density of WRC sites in this region. The frequency of R-loops is 1 in 25 alleles, regardless of the presence of the core Smu repeats, again consistent with the initiation of most R-loops upstream of the core repeats. These findings explain the surprisingly high levels of residual CSR in B cells from mice lacking the core Smu repeats but the marked reduction in CSR in mice with deletions of the region upstream of the core Smu repeats. These studies also provide the first analysis of how R-loop formation in the eukaryotic chromosome depends on the DNA sequence.
Feng-Ting Huang; Kefei Yu; Barbara B Balter; Erik Selsing; Zeliha Oruc; Ahmed Amine Khamlichi; Chih-Lin Hsieh; Michael R Lieber
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-06-11
Journal Detail:
Title:  Molecular and cellular biology     Volume:  27     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-07-31     Completed Date:  2007-09-06     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5921-32     Citation Subset:  IM    
Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, California 90089-9176, USA.
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MeSH Terms
B-Lymphocytes / metabolism
Base Sequence
Chromosomes, Mammalian / chemistry,  genetics*
Immunoglobulin Switch Region / genetics*
Immunoglobulin mu-Chains / genetics*
Lymphocyte Activation
Mice, Inbred C57BL
Recombination, Genetic / genetics
Ribonuclease H / metabolism
Sequence Deletion
Grant Support
Reg. No./Substance:
0/Immunoglobulin mu-Chains; EC H

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